The chronic use of phencyclidine (angel dust, PCP) has become a serious problem. The major focus of this grant is to elucidate the changes that occur in the brain with chronic phencyclidine use. Rats will be administered phencyclidine for long periods (up to one year) and brain regions will be analyzed for protein synthesis. Total protein synthesis and synthesis of discrete proteins will be monitored. For the latter, radiolabeled proteins will be separated on a modified two dimenional gel electrophoresis system which has recently been developed. The number of proteins altered and the magnitude of their alterations will be determined by visual inspection and by computer analysis of autoradiographs prepared from the control and experimental animals. An additional objective is to determine if chronic phencyclidine treatment alters brain morphology at the level of electron microscopy. The long term objective of this research is to understand, on a molecular level, the type of changes that occur in the brain with chronic phencyclidine use. Armed with this knowledge, it may be possible to design treatments for chronic users and those who overdose on the drug.